Brain Research最新文献

{"title":"Fuzhisan ameliorates cognitive ability in Alzheimer's disease by p62 and related autophagy regulatory pathways.","authors":"Zhaoxu Zhang, Shuangmei Zhang, Shen Liu, Yang He, Anrong Wang","doi":"10.1016/j.brainres.2024.149436","DOIUrl":"10.1016/j.brainres.2024.149436","url":null,"abstract":"<p><strong>Background: </strong>Maintaining autophagic homeostasis has been proved to play an important role in Alzheimer's disease.</p><p><strong>Object: </strong>The aim of this study was to investigate the effect of Fuzhisan(FZS) on autophagic function in Alzheimer's disease and to elucidate its potential mechanism through the P62 regulatory pathways.</p><p><strong>Methods: </strong>FZS was extracted by water extraction-rotary evaporation method. The novel object recognition test, morris water maze test and Y maze test were used to observe the cognitive and memory ability of APP/PS1 mice. The effects of FZS on the ultrastructure of mice hippocampus were examined by transmission electron microscopy. Molecular level changes were also further detected, including Aβ deposition, tau hyperphosphorylation, SOD, CAT and autophagy related proteins (p62, Nrf2, keap1, mTOR, LC3II/I, Beclin1, Atgs).</p><p><strong>Results: </strong>FZS could alleviate memory and cognitive impairment in APP/PS1 mice, increase the autophagic vesicles and organelle abundance in hippocampus. FZS also reduced the levels of Aβ and tau hyperphosphorylation in the hippocampus of model mice, upregulated the levels of SOD, CAT and autophagy related proteins (Nrf2, LC3II/LC3I, Beclin1, Atg7 and Atg12) as well as downregulated the expression of P62, keap1 and p-mTOR/mTOR proteins. Co-Ip results showed that FZS elevated the levels of p62/LC3 and P62-keap1-Nrf2 complex, but decreased the P62 and keap1 association.</p><p><strong>Conclusion: </strong>Our findings indicate that FZS may affect autophagy function and oxidative stress by regulating P62 and related pathways to promote the clearance of Aβ and phosphorylated tau, thereby improving the cognitive ability of AD, which provided a novel perspective for exploring the potential mechanism of FZS upon AD.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149436"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of traditional Chinese medicine Naofucong on diabetic cognitive impairment: Mechanisms involving insulin-degrading enzyme-mediated degradation of Amyloid-β and inhibition of ERK/JNK/p38 MAPK signaling pathway.","authors":"Yue Tian, Guangchan Jing, Ruiying Yin, Mei Ma, Weiwei Cao, Mengren Zhang","doi":"10.1016/j.brainres.2024.149365","DOIUrl":"10.1016/j.brainres.2024.149365","url":null,"abstract":"<p><p>The increasing prevalence of diabetes and its related cognitive impairments is a significant public health concern. With limited clinical treatment options and an incomplete understanding of the underlying mechanisms, traditional Chinese medicine (TCM) Naofucong is proposed as a potential neuroprotective agent against diabetic cognitive impairment (DCI). This study aims to investigate the therapeutic mechanisms of Naofucong in DCI. We hypothesize that Naofucong may improve cognitive function in diabetic rats by modulating the extracellular regulated protein kinases (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinases (MAPK) signaling pathway, enhancing insulin-degrading enzyme (IDE) expression, reducing amyloid-beta (Aβ) deposition, decreasing phosphorylated Tau (p-Tau) levels, and alleviating oxidative stress. Diabetes was induced in specific-pathogen-free male Sprague-Dawley rats using streptozotocin, and the rats were treated with oral Naofucong for 12 weeks. We assessed cognitive function and measured neuronal damage, oxidative stress injury, and the expression levels of IDE, Aβ, amyloid precursor protein (APP), p-Tau, and components of the ERK/JNK/p38 MAPK pathway. Diabetic rats showed significant declines in cognitive function, neuronal damage, oxidative stress, low IDE expression, Aβ accumulation, high APP expression, abnormal Tau phosphorylation, and overactivation of the ERK/JNK/p38 MAPK pathway. Naofucong treatment significantly reversed these symptoms. Our findings suggest that Naofucong improves cognitive impairment in diabetic rats by inhibiting the ERK/JNK/p38 MAPK pathway, upregulating IDE, reducing Aβ deposition, suppressing APP and p-Tau expression, and alleviating neuronal damage and oxidative stress. This research provides a reference for the clinical prevention and treatment of DCI using TCM Naofucong.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149365"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal protective effect of Artemisinin in ischemic stroke: Achieved by blocking lysine demethylase 1A-mediated demethylation of sphingosine kinase 2.","authors":"He Li, Ying Li, Yingju Wang, Yuchen Sheng","doi":"10.1016/j.brainres.2024.149442","DOIUrl":"10.1016/j.brainres.2024.149442","url":null,"abstract":"<p><p>Artemisinin (ART), a natural product isolated from the traditional Chinese plant Artemisia annua L., has shown neuroprotective properties in addition to its well-established antimalarial activities. This study investigates the therapeutic effect of ART in ischemic stroke (IS) and delves into its functional mechanism. Bioinformatics analyses revealed lysine demethylase 1A (KDM1A) as a promising target of ART aberrantly overexpressed in the context of IS. Increased KDM1A expression was detected in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated hippocampal neurons and transient middle cerebral artery occlusion (tMCAO)-challenged mice. Treatment with ART reduced KDM1A protein level, thus protecting mouse hippocampal neurons from OGD/R-induced oxidative stress and apoptosis. In vivo, ART reduced infarct size, reduced brain content, enhanced neurological function, and enhanced neuronal survival in tMCAO. Regarding the downstream cascade, KDM1A was found to repress transcription of sphingosine kinase 2 (SPHK2) by removing H3K4me2 modification near the SPHK2 promoter. Either KDM1A overexpression or SPHK2 knockdown abrogated the neuroprotective effects of ART. The ample evidence of this study suggests that ART fulfills neuroprotective functions in the context of IS by protecting SPHK2 from KDM1A-mediated transcription repression, highlighting ART as a promising regimen for the treatment of IS.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149442"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-enhanced delivery of resveratrol for targeted therapy of glioblastoma: Modulating the Akt/GSK-3β/NF-kB pathway in C6 glioma cells.","authors":"Gurpreet Singh, Paras Famta, Saurabh Shah, Ganesh Vambhurkar, Giriraj Pandey, Rahul Kumar, Prakash Kumar, Atul Mourya, Jitender Madan, Saurabh Srivastava, Dharmendra Kumar Khatri","doi":"10.1016/j.brainres.2024.149411","DOIUrl":"10.1016/j.brainres.2024.149411","url":null,"abstract":"<p><strong>Objective: </strong>The study aims to explore Resveratrol (RES) as a potential therapeutic agent for Glioblastoma multiforme (GBM), a challenging brain cancer. RES, a polyphenolic compound with known benefits in various diseases including cancer, has shown promise in inhibiting glioma progression through its effects on the AKT signaling pathways. However, its limited ability to cross the blood-brain barrier restricts its clinical application in GBM treatment. This study seeks to enhance efficacy of RES by developing RES-loaded nanoparticles designed to improve penetration into glioma cells and potentially overcome the blood-brain barrier, thereby enhancing therapeutic outcomes.</p><p><strong>Methods: </strong>Albumin nanoparticles were prepared and characterized using FT-IR, X-RD, and SEM to determine particle size. In vitro experiments were conducted using the C6 glioma cell line, employing MTT assays, Immunofluorescence, DC-FDA staining, and western blot analysis. Molecular docking studies were also performed to assess ability of RES to inhibit the AKT/GSK-3β/NF-kB pathway.</p><p><strong>Results: </strong>In vitro results demonstrated that RES-loaded nanoparticles induced apoptosis and reduced proliferation of C6 glioma cells compared to controls. Molecular docking studies confirmed RES's potential as an inhibitor targeting the AKT/GSK-3β/NF-kB pathway. Western blot analysis revealed downregulation of AKT and GSK-3β expression in cells treated with RES-loaded nanoparticles, accompanied by increased caspase 1 levels and decreased bcl2 expression, indicative of apoptosis.</p><p><strong>Conclusion: </strong>The findings suggest that RES effectively targets the AKT/GSK-3β/NF-kB signaling pathway in glioma cells. Furthermore, RES-loaded albumin nanoparticles significantly enhance therapeutic efficacy by improving cellular penetration, highlighting their potential in advancing GBM treatment strategies.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149411"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct contributions of BDNF/MEK/ERK1/2 signaling pathway components to whisker-dependent tactile learning and memory.","authors":"Hitomi Soumiya, Shingo Mori, Kohta Kageyama, Masateru Kawakami, Aoi Nara, Shoei Furukawa, Hidefumi Fukumitsu","doi":"10.1016/j.brainres.2024.149404","DOIUrl":"10.1016/j.brainres.2024.149404","url":null,"abstract":"<p><p>Whisker-mediated tactile perception is essential for rodent navigation, food acquisition, and social interactions. However, the molecular mechanisms underlying tactile information processing, learning, and memory have not been studied to the same extent as for other modalities. Using immunohistochemical staining, we investigated changes in regional c-Fos expression as an index of neuronal activity and phosphorylated (p)ERK1/2 as an index of ERK1/2 activity in mice trained on a tactile-cued 8-arm radial maze task. Over 12 trials, mice learned to selectively explore four baited arms covered with wire as the tactile cue while avoiding un-baited uncovered arms. The density of c-Fos⁺ cells was significantly higher in somatosensory cortex but not frontal cortex or amygdala of mice exposed to tactile cue - bait pairing compared to mice exposed to the same maze with all arms baited with or without tactile cues (unpaired conditions). The density of pERK1/2⁺ cells was also increased after paired trials 7 and 12 but not after paired trials 1 and 3 in frontal cortex, amygdala, and somatosensory cortex compared to mice exposed to the unpaired condition. The MEK1/2 inhibitor SL327 reduced c-Fos expression in frontal cortex and amygdala when applied during early trials, but impaired working memory when applied before later trials without affecting c-Fos expression. Heterozygous BDNF knockout mice exhibited impaired task learning and reduced pERK1/2 expression in frontal cortex and amygdala but not somatosensory cortex. These findings suggest that the BDNF/MEK/ERK1/2 pathway selectively promotes memory trace formation in frontal cortex and amygdala but not encoding in somatosensory cortex.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149404"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential molecular mechanisms of tobacco smoke exposure in Alzheimer's disease.","authors":"Yunqi Xie, Mingxue Yang, Haochen Wang, Yuting Chen, Xiaobo Shi, Huanwen Tang, Qian Sun","doi":"10.1016/j.brainres.2024.149394","DOIUrl":"10.1016/j.brainres.2024.149394","url":null,"abstract":"<p><strong>Background: </strong>Smoking is detrimental to health, with tobacco use being a critical factor in the development of various neurodegenerative diseases, including Alzheimer's disease (AD), which progressively impairs brain function and poses a significant threat to public health. This study aims to examine the potential genetic alterations induced by smoking that are associated with AD and to investigate the underlying regulatory mechanisms. The research will provide theoretical foundations for targeted prevention and treatment strategies for AD.</p><p><strong>Methods: </strong>This study analyzed datasets from the Gene Expression Omnibus (GEO) and the Comparative Toxicogenomics Database (CTD) to identify genes affected by tobacco smoke exposure and those altered in patients with AD relative to normal controls. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using OmicShare tools to screen for key pathways. Key genes were identified by constructing protein-protein interaction networks (PPI) in the STRING database with the aid of CytoHubba. Additionally, the binding activity of the proteins encoded by these key genes to nicotine, the main component of tobacco, was analyzed using molecular docking techniques. Finally, the analytical results were verified using Quantitative Real-Time Polymerase Chain Reaction.</p><p><strong>Results: </strong>The CTD identified 12,164 CE-related genes affected by tobacco smoke exposure. A comparison of these datasets yielded 94 common genes that were both influenced by tobacco and differentially expressed across all brain regions. The GO and KEGG pathway enrichment analyses showed that these common differentially expressed genes (DEGs) were predominantly enriched in the Wnt/β-catenin and PI3K-AKT signaling pathways. The DEGs' PPI network, constructed using the STRING database, highlighted key genes such as HSP90AB1, SOS2, MAGI1, and YWHAZ. Molecular docking studies demonstrated that nicotine binds effectively to the protein structures of these key genes, primarily through amino acid residues such as Ser and Glu. Experimental validation showed that HSP90AB1 and YWHAZ exhibited notable expression discrepancies under varying concentrations of cigarette smoke extract (CSE) treatments, particularly demonstrating a pronounced down-regulation trend at elevated concentrations.</p><p><strong>Conclusion: </strong>The study indicates that tobacco may impact the function of transmembrane transporter proteins and contribute to the development of AD by affecting key genes such as HSP90AB1 and YWHAZ, as well as signaling pathways like PI3K-AKT.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149394"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rTMS improves cognitive function and its real-time and cumulative effect on neuronal excitability in aged mice.","authors":"Chong Ding, Xueting Pan, Rui Fu, Haoyu Qiu, Haijun Zhu","doi":"10.1016/j.brainres.2025.149474","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149474","url":null,"abstract":"<p><p>Repetitive transcranial magnetic stimulation (rTMS) is acknowledged for its critical role in modulating neuronal excitability and enhancing cognitive function. The dentate gyrus of the hippocampus is closely linked to cognitive processes; however, the precise mechanisms by which changes in its excitability influence cognition are not yet fully understood. This study aimed to elucidate the effects on granule cell excitability and the effects on cognition of high-frequency rTMS in naturally aging mice, as well as to investigate the potential interactions between these two factors. It was observed that 20 Hz high-frequency rTMS attenuated granule cell loss in aged mice, demonstrating both cumulative and real-time effects on neural excitability. Importantly, this intervention significantly ameliorated age-related cognitive decline. The findings suggest that one of the potential mechanisms underlying the amelioration of age-related cognitive decline through high-frequency rTMS may involve the attenuation of granule cell apoptosis and the enhancement of their neural excitability.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149474"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the dual role of bilirubin in neurological Diseases: A Comprehensive exploration of its neuroprotective and neurotoxic effects.","authors":"Arshdeep Kaur, Rohit, Khadga Raj Aran","doi":"10.1016/j.brainres.2025.149472","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149472","url":null,"abstract":"<p><p>Neurodegenerative disorders are characterized by a progressive loss of neurons, causing substantial deficits in motor and cognitive functioning. Bilirubin is a yellow by-product of heme, existing in two primary isoforms namely unconjugated and conjugated, while initially produced unconjugated isomer is lipophilic and cytotoxic in nature. At physiological levels, bilirubin has an important role in brain function by acting as a powerful antioxidant, preventing brain tissues from oxidative damage by eliminating reactive oxygen species (ROS). Additionally, it contributes to immune regulation through microglial activation, cytokine release, complement system interception, fragment crystallization (Fc) receptor modulation, and major histocompatibility complex (MHC II) expression modification, which lower the risk of inflammatory and autoimmune reactions in the central nervous system (CNS). As per the literature, serum bilirubin concentrations are associated with CNS diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, hemorrhagic stroke, traumatic brain injury (TBI), multiple sclerosis (MS), epilepsy, schizophrenia and kernicterus spectrum disorder (KSD), which causes neuronal damage, especially in regions like the basal ganglia and cerebellum, which causes movement abnormalities and cognitive deficits. The aim of this article is to explore the dual role of bilirubin as neuroprotective and neurotoxic, essential for establishing effective therapeutic outcomes for neurodegenerative diseases by looking at its cellular mechanisms and discussing how bilirubin's antioxidant properties can shield neurons and, in some situations, may induce oxidative stress and apoptosis.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149472"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic stress-induced neuroplasticity in the prefrontal cortex: Structural, functional, and molecular mechanisms from development to aging.","authors":"Sami Awda Algaidi","doi":"10.1016/j.brainres.2025.149461","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149461","url":null,"abstract":"<p><p>Chronic stress profoundly affects the structure and function of the prefrontal cortex (PFC), a brain region critical for executive functions and emotional regulation. This review synthesizes current knowledge on stress-induced PFC plasticity, encompassing structural, functional, and molecular changes. We examine how chronic stress leads to dendritic atrophy, spine loss, and alterations in neuronal connectivity within the PFC, particularly affecting the medial PFC. These structural changes are accompanied by disruptions in neurotransmitter systems, most notably glutamatergic and GABAergic signaling, and alterations in synaptic plasticity mechanisms. At the molecular level, we discuss the intricate interplay between stress hormones, neurotrophic factors, and epigenetic modifications that underlie these changes. The review highlights the significant behavioral and cognitive consequences of stress-induced PFC plasticity, including impairments in working memory, decision-making, and emotional regulation, which may contribute to the development of stress-related psychiatric disorders. We also explore individual differences in stress susceptibility, focusing on sex-specific effects and age-dependent variations in stress responses. The role of estrogens in conferring stress resilience in females and the unique vulnerabilities of the developing and aging PFC are discussed. Finally, we consider potential pharmacological and non-pharmacological interventions that may mitigate or reverse stress-induced changes in the PFC. The review concludes by identifying key areas for future research, including the need for more studies on the reversibility of stress effects and the potential of emerging technologies in unraveling the complexities of PFC plasticity. This comprehensive overview underscores the critical importance of understanding stress-induced PFC plasticity for developing more effective strategies to prevent and treat stress-related mental health disorders.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149461"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological signatures of the effect of context on exploration: Greater attentional and learning signals when exploration is costly.","authors":"Thomas D Ferguson, Alona Fyshe, Adam White","doi":"10.1016/j.brainres.2025.149471","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149471","url":null,"abstract":"<p><p>Humans are excellent at modifying our behaviour depending on context. For example, humans will change how they explore when losses are possible compared to when they are not possible. However, it remains unclear what specific cognitive and neural processes are modulated when exploring in different contexts. Here, we had participants learn within two different contexts: in one the participants could lose points while in the other the participants could not. Our goal was to determine how the inclusion of losses impacted human exploratory behaviour (experiment one), and whether we could explain the neural basis of these effects using EEG (experiment two). In experiment one, we found that participants preferred less-variable choices and explored less often when losses were possible. In addition, computational modelling revealed that participants engaged in less random exploration, had a lower rate of learning, and showed less choice perseverance when losses were possible. In experiment two, we replicated these effects while examining a series of neural signals involved in exploration. During exploration, signals tied to working memory and learning (P3b), attention orienting (P3a) and motivation (late positive potential; an exploratory analysis) were also enhanced when losses were possible. These neural differences contribute to why exploratory behaviour is changed by different learning contexts and can be explained by the theoretical claim that losses recruit attention and lead to increased task focus. These results provide insight into the cognitive processes that underlie exploration, and how exploratory behaviour changes across contexts.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149471"},"PeriodicalIF":2.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}